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Brain metastases (BrMs) are poorly studied and likely underreported in diffuse pleural mesothelioma (DPM), limiting understanding of risk factors associated with their development. We evaluated the genomic, histologic, and clinical landscapes of patients with DPM and BrMs. We retrospectively reviewed all patients with a mesothelioma diagnosis treated at the Memorial Sloan Kettering Cancer Center between January 1, 2010, and May 1, 2025, with cross-sectional brain imaging. Clinicopathologic data and treatment outcomes were annotated for patients with BrMs. Among 194 patients with mesothelioma and brain imaging, 16 (8%) had BrMs. Half (n = 8) had tumors of epithelioid histology, 44% (n = 7) biphasic, and 6% (n = 1) sarcomatoid. Compared with our DPM cohort regardless of BrMs (n = 194) or a DPM cohort from The Cancer Genome Atlas (n = 74), patients with DPM and BrMs had a higher prevalence of LATS2 alterations (46% versus 7% versus 12%, respectively [p < 0.00001]). BrMs were typically (88%, n = 14) diagnosed after neurologic symptoms prompting imaging. Among patients with BrMs, the median overall survival from initial mesothelioma diagnosis was 35.4 (95% confidence interval, 19.3-not reached) months and 3.7 (95% confidence interval, 3.5-not reached) months from BrM diagnosis. Our findings suggest that BrM develops relatively late in DPM, is more common than previously reported, and may be enriched in patients with LATS2 alterations. Prospective, multi-institutional studies with standardized brain imaging are needed to further characterize the incidence of BrMs in DPM and associated risk factors. Routine brain surveillance at diagnosis and with symptoms should be considered for patients with DPM.

There is a paucity of data about patients with advanced NSCLC (aNSCLC) with disease control for at least 2 years since the start of first-line (1L) immunotherapy. Databases of five Israeli cancer centers were searched for cases of patients with aNSCLC who commenced 1L treatment with immunotherapy between 2018 and 2021 and had no progression of disease for at least 2 years since treatment initiation. Clinical, pathologic, and genomic sequencing data were retrospectively collected. The end of 2 years from the initiation of treatment was the index date. Progression-free survival (after 2 y) and overall survival (after 2 y) were calculated by Kaplan-Meier method from the index date. Collected variables were examined for correlation with the outcome. A total of 206 patients were included, with a median age of 65 years; 64.1% were males and 6.3% were never-smokers. Brain and liver metastases were found in 22.3% and 4.9%, oligometastatic disease in 80.6%; 62.1% had PDL1 greater than or equal to 50%. Mutations in STK11, KEAP1 and both were found in 3.9%, 0.5% and 0%. At a median follow-up of 25.0 months from the index date, the median Progression-free survival and overall survival after 2 years were not reached (NR) (95% confidence interval: NR-NR). There were 58 patients (28.2%) who progressed after the index date; 24 were rechallenged with immunotherapy. Response to rechallenge was 50%. In multivariate analysis, older age, squamous histologic diagnosis, and liver metastasis were associated with increased risk of death. In real-life settings, aNSCLC (at 2 years or longer) who are responders to 1L immunotherapy have high rates of oligometastatic disease, high PDL1, low rates of never-smoking history, baseline liver metastasis, and STK11 or KEAP1 mutations. Except for age, histologic diagnosis, and liver metastasis, long-term survival is not correlated with baseline variables. Approximately a quarter of progress after 2 years of disease control.

Data from two global protocols under the expanded access program, Study-436 and Study-442, evaluating the safety and efficacy of sotorasib in patients with advanced KRAS G12C-mutated NSCLC beyond the traditional registrational trial setting are presented. Patients were enrolled in 90 centers globally. Baseline characteristics and safety data for Study-436 and Study-442 and efficacy data for Study-436 were estimated. All data were summarized descriptively. A total of 268 patients (n = 150 [Study-436] and n = 118 [Study-442]) received oral sotorasib (960 mg daily). At baseline, 21.3% and 31.0% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) 2 and a history of central nervous system (CNS) metastases, respectively.Treatment-related adverse events occurred in 64.9% of patients; diarrhea (31.3%) was the most common. The incidence of treatment-related adverse events was similar between patients with ECOG PS 0 to 1 (67.8%) and PS 2 (54.4%) and those with (69.9%) and without (62.7%) a history of CNS metastases. The median real-world progression-free survival and overall survival was 6.3 and 9.5 months, respectively. The median real-world progression-free survival was numerically similar in patients with ECOG PS 0 to 1 versus PS 2 (6.5 versus 5.6 mo) and in patients with versus without a history of CNS metastases (5.7 versus 6.5 mo); median overall survival followed similar trends. Improvement from ECOG PS 2 to ECOG PS 0 to 1 was observed by the end of first cycle of treatment (57.9%). Safety and efficacy outcomes of sotorasib in this study were not affected with ECOG PS 2 and the history of CNS metastases and were consistent with those reported in key clinical trials.

Trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are HER2-targeting antibody-drug conjugates (ADCs) with activity in HER2-mutant non-small cell lung cancer (NSCLC). Whether patients benefit from sequential HER2-directed ADCs therapy remains unknown. We conducted a single-center retrospective study of patients with HER2-mutant NSCLC who received both T-DXd and T-DM1 in either order. Clinical characteristics, confirmed overall response rate, real-world progression-free survival (rwPFS), and overall survival (OS) were evaluated. All time-to-event endpoints were calculated from the start of the second ADC. Twenty-five patients were identified: 17 received T-DM1 post-T-DXd and 8 received T-DXd post-T-DM1. The median age for the entire cohort was 67 years; 56% were female. Most patients (21/25, 84%) harbored HER2 kinase-domain mutations, while 3 had extracellular and 1 had transmembrane domain alterations. The median number of prior systemic therapies before the second ADC was three. Seventeen patients (68%) received the two ADCs in direct sequence without other intervening therapies. In the T-DM1 post-T-DXd cohort, the median rwPFS was 3.3 months (95% CI, 1.9-5.6) and the median OS was 9.2 months (95% CI, 4.9-NR). No confirmed responses were observed; however, two patients (12%) achieved unconfirmed partial responses, and one had prolonged stable disease for 13.9 months. In the T-DXd post-T-DM1 cohort, the median rwPFS was 5.2 months (95% CI, 4.1-NR) and the median OS was 25.0 months (95% CI, 8.2-NR); three patients (37.5%) achieved confirmed partial responses. T-DXd retains clinical activity after prior T-DM1 use, whereas T-DM1 has limited efficacy after prior T-DXd in HER2-mutant NSCLC. Understanding the mechanisms of response and resistance to ADCs will hopefully help to inform treatment strategies using sequential ADCs in lung cancer and other malignancies.

Recurrent extensive-stage SCLC (ES-SCLC) remains a major therapeutic challenge. Although immune checkpoint inhibitors (2Ls), bispecific antibodies, and antibody-drug conjugates offer promise in early lines, outcomes beyond the second line (2L) remain poor. Real-world data on third line (3L) treatment patterns, clinical outcomes, and quality of life (QoL) after ICI-based first line (1L) therapy are limited but critical to inform clinical decision-making. CRISP is a prospective, multicenter registry for patients with lung cancer in Germany. In-depth patient and tumor characteristics, details about treatments, outcome, and patient-reported outcomes data are collected. Between September 2019 and April 2021, 114 sites in Germany recruited 518 patients with ES-SCLC, of which 82 started 3L therapy. Of 82 patients, 58.5% were male and 79.3% were below 70 years old. At 3L start, Eastern Cooperative Oncology Group performance score was 0 in 18.3%, 1 in 39.0%, and more than or equal to 2 in 19.5% (23.2% unknown). In the 1L setting, 68 patients (82.9%) received platinum-based chemotherapy plus ICI and 68 (82.9%) were platinum refractory (time to next treatment < 3 mo). Furthermore, 2L therapy consisted of topotecan (47.6%) and other chemotherapies (52.4%). The three most common 3L regimens were paclitaxel (22%), topotecan (22%), and cyclophosphamide, doxorubicin, vincristine (17.1%). Local radiotherapy was used in 19 patients (23.2%) in the 3L. Median real-world progression-free survival was 2.2 months (95% confidence interval: [1.8-3.0]), and real-world overall survival was 4.4 months (95% confidence interval: [3.4-5.2]). Exploratory analyses revealed numerically longer real-world overall survival with increasing time between 1L and 2L initiation (<6 mo: 3.4 mo; 6-11 mo: 4.4 mo; &#x2265; 12 mo: 8.3 mo) and in patients with Eastern Cooperative Oncology Group performance score 0 to 1 versus more than or equal to 2 (5.1 versus 4.4 mo). QoL, assessed by FACT-L subscales, remained stable during follow-up. Outcomes in 3L therapy in ES-SCLC remain poor among subgroups, even in predominantly ICI-pretreated patients, strongly highlighting the need for better 3L strategies. Although QoL can be preserved, therapeutic efficacy is lacking. These real-world data are critical to support shared decision-making, helping clinicians and patients weigh the limited benefits of further chemotherapy against best supportive care.

ALK fusion-positive NSCLC is driven by a range of fusion partners, most often EML4::ALK. The clinical impact, oncogenicity, and resistance mechanisms of rare, noncanonical ALK fusions remain underexplored. We describe two previously unreported ALK fusion partners in NSCLC and explore the potential mechanisms of resistance in each case, including on-target and bypass mutations, as well as the use of next-generation sequencing (NGS) testing on cerebrospinal fluid (CSF) as a useful tool. We report two patients with metastatic NSCLC harboring novel ZFPM2::ALK and TRIM24::ALK fusions. Both patients achieved marked partial responses to first-line alectinib, confirming the oncogenic and actionable nature of the fusions. The patient with ZFPM2::ALK fusion developed leptomeningeal disease after 27 months; CSF NGS revealed persistent fusion and newly acquired CDKN2A/B deletion. The patient with TRIM24::ALK fusion, following durable responses to alectinib and lorlatinib, relapsed with detection of on-target ALK kinase domain mutations (F1174V, I1171N) and MYC amplification on progression. These cases expand the landscape of noncanonical ALK fusions in NSCLC which are responsive to approved ALK TKIs and offer insights into oncogenic and resistance mechanisms. Comprehensive molecular workup, including RNA-based NGS, is essential for detecting rare but actionable ALK rearrangements and optimizing therapeutic strategy. NGS of CSF was a valuable tool for the detection of clinically suspected leptomeningeal disease and disease monitoring.

Thymic malignancies are primarily managed with surgery. Some patients are medically inoperable or technically unresectable. We report the characteristics and outcomes of patients with unresected thymic tumors treated with definitive radiation therapy (RT) at our institution. Patients treated with curative-intent RT for unresected thymic tumors between 1997 and 2023 were identified. Age at diagnosis, sex, histology, Masaoka or TNM stage, WHO classification, reason for no resection, RT dose and fractionation, presence of paraneoplastic syndrome, chemotherapy use, and toxicities were extracted. Overall and local failure-free survival, patterns of progression, and treatment toxicities were assessed. This retrospective chart review did not require informed consent. A total of 33 consecutive patients were identified (16 females and 17 males) with a median age of 61 years at diagnosis. Overall, 22 patients had thymoma and 11 had thymic carcinoma. T stage was T2 (one), T3 (seven), and T4 (25); N stage was N0 (15), N1 (one), and N2 (17); M stage was M0 (21), M1a (eight), and M1b (four). Median tumor size was 8.1 cm. Three patients were medically inoperable; 30 were technically unresectable. Of the 33 patients, 29 received chemotherapy. The median RT dose was 60 Gy in 2 Gy fractions.Furthermore, 6% developed a grade 3 toxicity and 9% developed grade 2 pneumonitis. No grade 4/5 toxicities were observed. The 2-year overall survival was 69% (95% confidence interval [CI]: 52-92) and 5-year overall survival was 56% (95% CI: 37-85). The 3- and 5-year local failure rates were 20% (95% CI: 6.9-39). In the most advanced stage and one of the largest reports to date, definitive chemo-RT provides high rates of local control in patients with unresected thymic malignancies.

Thymic epithelial tumors, including thymomas and thymic carcinomas (TC), are rare thoracic malignancies with poor prognosis in advanced stages. Platinum-based chemotherapy (CT) remains the first-line standard with limited efficacy. Novel systemic therapies, such as immune checkpoint inhibitors (ICIs) and antiangiogenic agents, have exhibited promise in refractory disease. A systematic search of PubMed, EMBASE, and Cochrane was performed for studies including patients with unresectable, recurrent, or metastatic thymic epithelial tumors treated with platinum-based CT combined with ICIs or antiangiogenic agents. Meta-analyses were conducted using a random-effects model, with heterogeneity assessed through the I 2 statistic and Cochran's Q test. Nine studies encompassing 208 patients were included, of which 93.7% had TC. The data set comprised five phase II trials and four retrospective cohorts. The pooled 12-month overall survival rate was 96.08% (95% confidence interval [CI]: 84.80-99.08), and 12-month progression-free survival was 56.68% (95% CI: 45.82-70.44). The median duration of response and median progression-free survival were 11.96 (95% CI: 6.32-22.64) months and 16.22 (95% CI: 10.30-25.52) months, respectively, with a pooled objective response rate of 57.69% (95% CI: 43.99-70.3). The objective response rate was 68.50% for antiangiogenic and 51.19% for ICIs combinations. Any-grade treatment-related adverse events occurred in 88.65%, grade 3 or higher in 30.22%, and grade 3 or higher immune-related adverse events in 11.62%, with treatment discontinuation in 13.55%. Platinum-based CT combined with ICIs or antiangiogenic agents exhibits promising efficacy and manageable toxicity, particularly in TC. Evidence in thymomas remains limited, and severe immune-related toxicity warrants caution. Randomized trials are needed for confirmation.

The discovery of EGFR mutations two decades ago launched an era of rapid development and clinical application of targeted therapies in NSCLC. Today, increasing numbers of targeted therapies against somatic aberrations involving nine different genes have become available for treating patients with lung cancer and have improved their outcomes. However, acquired resistance and tumor tolerance to these therapies remains one of the biggest challenges in lung cancer treatment today. Most, if not all, targeted therapies have limited durability, which we now recognize is due to both genetic and non-genetic mechanisms of resistance. The state of our current understanding of resistance and new approaches to prevent or overcome resistance were recently presented at the International Association for the Study of Lung Cancer Hot Topics Meeting. Here, we summarize and discuss the emerging concepts and new strategies for combating drug tolerance and resistance in targeted therapies, including our understanding of the role of genetics, drug-tolerant persister cells, tumor plasticity and lineage transformation, spatial and temporal heterogeneity, microenvironmental influence, and novel therapeutic approaches.

Neuroendocrine neoplasms represent a rare and poorly understood collection of malignancies. A better understanding of their biology is needed to improve treatment options. Male predominance to the incidence of neuroendocrine neoplasms of the thymus suggests a biological basis for this observation. This single-institution, retrospective cohort study evaluated androgen receptor (AR) expression and other clinicopathologic features in thymic neuroendocrine neoplasms compared with thymic epithelial tumors and neuroendocrine neoplasms of other sites. Expression of neuroendocrine and prostate markers was also assessed. For further molecular characterization, copy number analysis of AR and other relevant genes was assessed by single nucleotide polymorphism array. Last, analysis of single genes and thymic epithelial gene sets was performed using published thymic tumor transcriptomes. A cohort was assembled from 17 patients with neuroendocrine malignancies of primary thymic origin with assessable tissue for immunohistochemical analysis. The cohort was predominantly male (12 males, five females). Immunohistochemical analysis of the AR demonstrated positive staining in nine cases, all of which were male. Compared with thymic neuroendocrine neoplasms, AR expression is considerably less frequent in thymomas, thymic carcinoma, and neuroendocrine neoplasms of other sites of origin. No relevant copy number changes in the AR were identified. Further molecular characterization revealed expression of ASCL1 and limited expression of common prostate lineage and differentiation markers within our cohort, including thymic neuroendocrine epithelial gene set enrichment in published transcriptomes of thymic neuroendocrine neoplasms. The AR is expressed in a considerable fraction of thymic neuroendocrine neoplasms and is associated with male predominance. This observation has implications for investigation of androgen deprivation and receptor blockade.

Extensive-stage SCLC (ES-SCLC) is a highly aggressive type of lung cancer with a high risk of early progression and limited survival. Standard of care for first-line treatment is platinum-etoposide chemotherapy plus anti-PD-L1 immune checkpoint inhibitors. Intergroupe Francophone de Canc&#xe9;rologie Thoracique-1905 CLINATEZO is a nationwide, non-interventional, retrospective study of consecutive patients with ES-SCLC who received atezolizumab plus platinum-based chemotherapy as part of the French Early Access Program that ran from May 2019 to March 2020. In this analysis, predictors of long-term response (defined by a real-world progression-free survival [rwPFS] > 12 mo) and long-term survival (defined by an overall survival [OS] > 24 mo) were assessed. A total of 517 patients were enrolled from 65 centers. After a median follow-up of 53.8 months, median, 12-month, and 48-month rwPFS rates were 5.2 (95% confidence interval [CI]: 5.0-5.4) months, 14.6% (95% CI: 11.6-17.9), and 6.8% (95% CI: 4.7-9.4), respectively. Median, 24-month, and 48-month OS rates were 11.3 (95% CI: 10.1-12.4) months, 21.1% (95% CI: 17.7-24.8), and 11.4% (95% CI: 8.8-14.4), respectively.Long-term response was observed in 12.6% patients. Median OS was 9.7 months in patients with rwPFS less than or equal to 12 months and 53.7 months in patients with rwPFS more than 12 months. Baseline characteristics associated with rwPFS more than 12 months were being a former smoker (versus current smoker, p = 0.003) and having an Eastern Cooperative Oncology Group performance status of 0 to 1 (versus 2, p = 0.048).Long-term survival was observed in 20.5% patients. Median OS was 8.8 months in patients with OS less than or equal to 24 months and 52.9 months in patients with OS more than 24 months. Predictors of long-term survival were younger age (p = 0.030), limited stage at initial diagnosis of SCLC (p = 0.022), and previous line of platinum-based chemotherapy (p = 0.01). CLINATEZO demonstrates the reproducibility of the key survival outcomes of landmark trials, in a real-life setting, for patients with ES-SCLC. Only low smoking history and performance status were associated with long-term response in our cohort.

Patients with unresectable locally advanced NSCLC who are not candidates for concurrent chemoradiation represent an unmet medical need. We report long-term results for this patient subgroup from two phase III trials. We analyzed data from patients with locally advanced NSCLC in the EMPOWER-Lung 1 (NCT03088540) and EMPOWER-Lung 3 (NCT03409614) studies. In EMPOWER-Lung 1, patients were randomized 1:1 to first-line (1L) cemiplimab monotherapy or chemotherapy with more than or equal to 50% programmed death-ligand 1 expression. In EMPOWER-Lung 3, patients were randomized 2:1 to 1L cemiplimab plus chemotherapy or chemotherapy, regardless of programmed death-ligand 1 expression. Patients with locally advanced NSCLC constituted 15% of the overall study populations. With cemiplimab monotherapy, the overall survival (OS) was improved versus chemotherapy (median 26.1 versus 13.9 mo; hazard ratio [HR]: 0.67, 95% confidence interval [CI]: 0.38-1.17) and progression-free survival (8.1 versus 6.2 mo; HR: 0.56, 95% CI: 0.34-0.95). With cemiplimab plus chemotherapy, the OS was improved versus chemotherapy alone (24.1 versus 13.8 mo; HR: 0.50, 95% CI: 0.27-0.95) and progression-free survival (12.5 versus 6.2 mo; HR: 0.34, 95% CI: 0.19-0.61). Treatment-emergent adverse events grade more than or equal to 3 occurred in 37.8% (cemiplimab) and 53.7% (chemotherapy) in EMPOWER-Lung 1 and in 46.7% (cemiplimab plus chemotherapy) and 25.0% (chemotherapy) in EMPOWER-Lung 3. Favorable patient-reported outcomes were observed with cemiplimab monotherapy than chemotherapy; no significant patient-reported outcomes favoring chemotherapy were observed in either study. This subgroup analysis supports the clinical benefit of 1L cemiplimab as monotherapy or combined with chemotherapy in patients with unresectable locally advanced NSCLC (not candidates for definitive chemoradiotherapy).

Concurrent chemoradiotherapy (cCRT) is the standard of care for unresectable stage III NSCLC, but whether EGFR mutation is a prognostic factor remains unclear. This study evaluated the efficacy and safety of cCRT in unresectable stage III EGFR-mutant NSCLC. This study aimed to describe and compare the efficacy and safety outcomes of patients with unresectable stage III NSCLC treated with cCRT in those with and without EGFR mutation. Data from three randomized phase II trials in the Japan Lung Cancer Society database (n = 274; 116 EGFR mutant, 158 EGFR wild type) were analyzed. Outcomes were progression-free survival (PFS), overall survival, and safety. Patients with EGFR-mutant NSCLC exhibited significantly shorter PFS than patients with EGFR wild-type NSCLC (hazard ratio [HR] = 1.38; 95% confidence interval [CI]: 1.05-1.82; p = 0.021). The results were generally consistent without statistical deviation, regardless of subgroup characteristics. EGFR mutation was retained as a covariate in the final multivariate model for PFS (HR = 1.358; 95% CI: 0.977-1.886; p = 0.068). Overall survival was not significantly different between the groups (HR = 0.98; 95% CI: 0.70-1.38; p = 0.903). A higher incidence of grades 3 to 4 pneumonitis was observed in patients with EGFR-mutant NSCLC compared with patients with EGFR wild-type NSCLC (7.8% versus 2.6%). Patients with EGFR-mutant unresectable stage III NSCLC exhibited significantly shorter PFS than patients with EGFR wild-type NSCLC. The median PFS was generally consistent with that of the control arm in the LAURA trial. Increased pneumonitis risk necessitates close monitoring in patients with EGFR-mutant unresectable stage III NSCLC.

Tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3 on T cells, has generated impressive treatment response rates in relapsed extensive-stage SCLC and large cell neuroendocrine carcinoma. We performed a retrospective, multi-institutional analysis of 48 patients who received tarlatamab as standard of care to assess how safety and efficacy outcomes translate into real-world practice. Rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 54% and 33%, respectively, with most being grades 1 to 2 in severity (100% and 87.5%). Of the 30 patients included in our efficacy analysis, the best overall response rate was 67% and disease control rate was 73%. With median follow-up of 5.7 months, median progression-free survival was 4.9 months (95% confidence interval: 4-not reached) and median overall survival was not reached (95% confidence interval: 4.8-not reached). Nine patients underwent molecular response assessment, with circulating tumor DNA trends corresponding with radiographic response. In this multicenter cohort study, tarlatamab continued to demonstrate encouraging response rates and progression-free survival; however, differences were observed in rates and timing of key treatment-associated toxicities compared with previous trial data.

Lung cancer is the most common non-acquired immunodeficiency syndrome-defining cancer in people living with human immunodeficiency virus (PLWH). PLWH were initially excluded from clinical trials of immune checkpoint inhibitors (ICIs) because of safety and efficacy concerns; little is known about real-world rates of immune-related adverse events (irAEs) and outcomes in PLWH with lung cancer treated with ICIs. Adults (age &#x2265;18 y) diagnosed with lung cancer and treated with ICIs between 2015 and 2021 were identified from the Merative MarketScan database. Patients were stratified into the following two cohorts: PLWH and PLWoH (people living without human immunodeficiency virus). We evaluated rates of irAEs and estimated overall survival (OS) between groups with Kaplan-Meier survival analysis; survival function was calculated from ICI initiation to death or last follow-up. We used the log-rank test to assess statistical differences in survival between cohorts. Of the 21,259 people with lung cancer treated with ICIs, 105 were identified as PLWH. There was no significant difference in median OS of PLWH versus PLWoH (343 versus 364 days, p = 0.62). PLWH experienced a similar rate of irAEs (59.1%) as PLWoH (58.8%). The most common irAEs in PLWH were neurologic (35.48%), endocrine (33.87%), renal (24.19%), and cardiac (24.19%), versus endocrine (47.69%), renal (28.80%), cutaneous (25.22%), and cardiac (24.39%) in PLWoH. Patients who experienced irAEs had significantly improved OS in both cohorts versus those without irAEs (both p < 0.0001). We found similar rates of irAEs and OS in real-world populations of PLWH and PLWoH with lung cancer treated with ICIs. Further research is needed to identify predictors of toxicities.

Lung cancer is a heterogeneous and complex disease requiring multidisciplinary input for optimal management planning, with guidelines recommending that all patients be discussed in a multidisciplinary setting. Multidisciplinary meeting (MDM) discussion aims to enhance evidence-based management, improve treatment access, and optimize complex management plans. We aimed to assess the extent and impacts of MDM discussion in patients with lung cancer described by the Victorian Lung Cancer Registry from 2011 to 2023 in Victoria, Australia. We identified MDM-presented and nonpresented patients and assessed the impacts of MDM presentation. OR and survival hazard ratios were assessed using Cox proportional regression analysis. Survival analysis was determined using the Kaplan-Meier product-limit method. Sensitivity analyses were conducted using landmark analysis and propensity score matching methods. A total of 18,597 patients were included, of whom 67% had evidence of presentation to a lung cancer MDM, with MDM presentation increasing from 59.1% to 80.6% during the study period. MDM presentation was associated with higher levels of provision of guideline-concordant treatment in NSCLC (56.2% versus 44.5%, p < 0.001), and lower levels of no treatment (10.0% versus 21.4%, p < 0.001). Modifiable factors that could increase MDM presentation include referral of patients of older age, stage IV disease, SCLC, and diagnosis at a private or regional hospital. Propensity-matched survival analysis in NSCLC revealed a median survival of 1.1 years for MDM-presented versus 0.86 years for nonpresented individuals, providing a 12% reduction in mortality hazard (hazard ratio 0.88 [0.82-0.95], p < 0.001). During the period of activity of the Victorian Lung Cancer Registry, MDM presentation increased from 59.1% to 80.6%. Management outcomes in MDM-presented patients identified multiple underserved cohorts and revealed considerable increases in treatment modalities and guideline-concordant treatment in NSCLC in this observational study, with an associated 12% improvement in survival advantage overall.

Immune checkpoint inhibitors (ICIs) are increasingly being used to treat lung cancer perioperatively. Although ICI use has led to long-term improvements in patient outcomes, its high costs have increased medical expenses. We evaluated the cost-effectiveness of perioperative ICI therapy for NSCLC in Japan, the USA, and Brazil. Hazard ratios of disease-free survival and overall survival for neoadjuvant or adjuvant chemotherapy and neoadjuvant, adjuvant, or neoadjuvant plus adjuvant therapy with ICI were estimated from landmark phase III trials using a network meta-analysis. A partitioned survival model was used to estimate quality-adjusted life-years and life-years. Drug and hospitalization costs were included using standard regimens as of April 2023, discounted at 2% annually. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years for neoadjuvant chemotherapy compared with no perioperative treatment was &#xa5;714,940 ($4468) in Japan. That for neoadjuvant therapy by ICI compared with neoadjuvant chemotherapy was &#xa5;5,285,770 ($33,036). The ICERs for other regimens were not calculated because of their dominance. In the USA and Brazil, the ICERs for neoadjuvant chemotherapy were $32,726 and $29,320, respectively, whereas those for neoadjuvant therapy with ICI were $228,467 and $92,573, respectively. The ICER threshold in Japan is generally &#xa5;5 million and &#xa5;7.5 million for essential drugs such as anticancer agents. The ICER of neoadjuvant chemotherapy was lower than the former threshold, whereas that of neoadjuvant nivolumab was lower than only the latter threshold. Therefore, neoadjuvant chemotherapy is cost-effective in Japan, the USA, and Brazil, whereas neoadjuvant nivolumab is only cost-effective in Japan.

Immune checkpoint inhibitor (ICI) clinical trials generally enroll non-Hispanic White patients at academic or private practice settings. ICI outcomes at safety-net settings and across diverse populations remain limited. We conducted a retrospective study of patients with advanced NSCLC treated in a safety-net health care system and at an academic cancer center. We obtained clinical and demographic data from the electronic medical record. Kaplan-Meier estimates and Cox proportional hazards model were used to assess variables associated with survival. A total of 408 patients were included. Compared with the academic center cohort (n = 213), the safety-net cohort (n = 195) was younger (35% versus 75% &#x2265; 65 y old; p < 0.001), had more racial and ethnic diversity (48% versus 73% non-Hispanic White; p < 0.001), and had more disadvantaged socioeconomic score (61 versus 24 median socioeconomic index; p < 0.001). After multivariable adjustment, patients receiving ICI as part of their treatment had improved survival compared with patients receiving chemotherapy alone (chemoradiation and ICI: adjusted hazard ratio [aHR] = 0.54; 95% confidence interval [CI]: 0.31-0.93; p = 0.03; chemotherapy and ICI: aHR = 0.44; 95% CI: 0.28-0.68; p < 0.001; ICI alone: aHR = 0.53; 95% CI: 0.30-0.91; p = 0.02). There was a near significant association with improved survival at academic practice setting (HR = 0.77; CI = 0.58-1.03; p = 0.08). There were no differences in survival according to race and ethnicity or socioeconomic status. In a diverse cohort across practice settings, receipt of ICI was associated with improved survival, regardless of facility type, race and ethnicity, or socioeconomic status. Efforts to provide ICI access to all eligible patients may improve outcomes.